The applicant is a neurologist and movement disorders specialist with three years of post-fellowship, faculty experience involving clinical care, clinical trials, and clinical research into etiologic risk factors for PD including genetic factors. The goal of this career development award is to provide the applicant with comprehensive training in genetic epidemiology through course work, individual tutorials, and practical application of gene mapping techniques to a multi-incident Amish family with Parkinson Disease (PD). PD is a neurodegenerative disorder that produces substantial disability for nearly 1 million people in North America. There is no known cause of the disease in the majority of patients; however, a genetic etiology has been found in a few rare multi-incidence families. Identification of such genes and subsequent determination of the cell biological effects of these mutations will provide important clues to the pathophysiology. Each new mutation discovered adds critical converging evidence about pathophysiological mechanisms common to all to those affected with PD. We have identified 27 members of a large Amish family with clinically typical PD and have excluded known PD genetic mutations. However, we still need to prove that PD is inherited in this pedigree. We will use two different methods to prove that PD in this kindred has a genetic basis. The first approach will assume an autosomal recessive model of inheritance and use genetic marker data provided by CIDR on our subjects to perform homozygosity mapping. A second approach will be to calculate a kinship coefficient to determine if the affected members of the pedigree are "more related" than randomly selected age-matched individuals from the same population. Finally, we will test whether [18]FDOPA PET permits the conversion of some people identified clinically as possible or probable PD in to PET-confirmed PD and thereby functioning as an endophenotype for disease state. This family provides a unique opportunity for the candidate to become a productive independent investigator in genetics of Parkinson Disease and other movements disorders and to develop skills needed for interpretation of [18]FDOPA PET.